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Earth's ocean, the planet's life-support system, is experiencing rapid and widespread transformations that extend far below its surface. A promising international study published in Nature Climate Cha...

Oliver has an inherited condition called Hunter syndrome, which causes progressive damage to the body and brain.

Summary note from a workshop on how the UK can adapt to international climate change risks.

The anaerobic glycyl radical enzyme choline trimethylamine-lyase (CutC) is produced by multiple bacterial species in the human gut microbiome and catalyzes the conversion of choline to trimethylamine (TMA) and acetaldehyde. CutC has emerged as a promising therapeutic target due to its role in producing TMA, which is subsequently oxidized in the liver to form trimethylamine-N-oxide (TMAO). Elevated TMAO levels are associated with several human diseases, including atherosclerosis and other cardiovascular disorders─a leading cause of mortality worldwide. Understanding the catalytic mechanism of this enzyme should aid successful design of potent inhibitors. Here, we employed extensive molecular dynamics (MD) simulations to reveal that hydrogen bonding within the CutC active site plays a crucial role in orienting choline for the initial pro-S hydrogen abstraction, leading to the formation of the α-hydroxy radical. The reaction mechanism was explored with quantum mechanics/molecular mechanics (QM/MM). The performance of three density functionals (B3LYP-D3, ωB97X-D3, and M06–2X) was tested against DLPNO–CCSD(T) ab initio calculations. These results indicate that choline cleavage occurs via TMA migration leading to a stable product carbinolamine which likely undergoes 1,2-elimination to acetaldehyde and TMA in water. Mechanistic insights consistently support the TMA migration pathway over direct TMA elimination, providing clear evidence for the preferred reaction mechanism. Two distinct mechanistic pathways were identified: one with a relatively high activation energy barrier, and the other with a lower barrier which is in a good agreement with the previously reported experimental kinetic parameters. QM/MM MD simulations further confirm that Glu491 functions as a catalytic base, abstracting a proton from the α-hydroxy radical and thereby facilitating the experimentally observed C–N bond cleavage. The relative binding affinity of the reactant (choline) and product (carbinolamine) was estimated with alchemical relative binding free energy calculations, complemented by noncovalent interaction analysis. These results elucidate the molecular basis for differences in their interactions with CutC (particularly highlighting key electrostatic interactions with Asp216 and Glu491) providing insights for future inhibitor design.

In these financially straitened times, funders must recognize that great discoveries often arise from work that was looking for something completely different.

As anti-science leaves research reeling, does evidence-based policy have a future?

Study of Met Office data one of first to show how nocturnal insects affected by factors such as light pollution Scientists have used Met Office radar data to track the trillions of insects flying above the UK for the first time, revealing a concerning decline in nocturnal species. The team repurposed data from the UK’s network of 15 weather surveillance radars, which scan the sky hundreds of times a day. Continue reading...

AQuaRef employs machine learning to refine protein structures from cryo-EM and X-ray data in Phenix. It achieves quantum-level precision, improving model geometry and fit to the data while reducing ov...

Qubit Pharmaceuticals is a French-American deeptech startup, focusing on discovering novel molecules for complex targets in healthcare and materials science. We leverage proprietary molecular simul...

Biodiversity losses are growing, the IUCN reports as summit opens, but green turtle’s recovery ‘reminds us conservation works’

The Nobel Prize rewards science, humanism and peace efforts. This is one of the central concepts in the will of Alfred Nobel, and it also permeates the outreach activities that have been developed for...

Structural and computational studies indicate the presence of a haem-lysine double crosslink in Methylococcus capsulatus cytochrome P460.

Supplementary information for the project 'Climate Change: Evidence and causes'.

RFK Jr has vowed to find out what’s responsible, but scientists say he is ignoring answers from decades of research.

Global survey of corporate executives shows capital investment in sustainability and climate risk efforts is increasing - and so are the financial returns